Lapatinib，别名: GW572016, GSK572

产品描述

Lapatinib is a dual inhibitor of Lapatinib is a dual ErbB2/EGFR (IC50: 9.2/10.8 nM) inhibitor

靶点活性

C-Raf-1,>10μM

c-Src,3.5μM

EGFR,10.8nM

HER2/ErbB2,367nM

实验溶液

15% Captisol: 30 mg/mL

体外活性

培养HN5 细胞群2周（不加 Lapatinib ）左右后，再加30 μM Lapatinib 短暂处理，细胞生长完全被抑制。浓度>3.3 μM时，抑制率达50%；浓度为0.37 μM时，抑制率达20%。另一种细胞A-431（EGFR过量表达）与HN5反应类似。在抑制 EGFR过量表达的细胞生长方面，Lapatinib与 OSI-774 相似。除ErbB-4外, Lapatinib 对EGFR 和 ErbB-2的选择性比其他测试激酶高300多倍，如c-Src, MEK和ERK。Lapatinib抑制EGFR 和ErbB-2受体自磷酸化的作用存在剂量依赖性，对BT474 和HN5 细胞的IC50 分别为 0.17 和0.08 μM。作用于EGFR-和ErbB-2-过量表达的肿瘤细胞时，Lapatinib的抑制作用比作用于上述纯化酶的效力低10倍左右。Lapatinib 抑制 EGFR- 和ErbB-2过量表达的细胞生长，而EGFR选择性抑制剂OSI-774和 Iressa则会优先抑制 EGFR过量表达的细胞生长。Lapatinib对肿瘤细胞的作用比正常成纤维细胞效果高约100倍。ErbB-2转染后的乳腺上皮细胞HB4a c5.2对 Lapatinib的敏感度比未转染的亲本细胞高40倍左右。

体内活性

实验对象：肿瘤携带小鼠。给药剂量：30和 100 mg/kg ，2次/天，口服。实验结果：以剂量依赖的方式抑制肿瘤生长。100 mg/kg Lapatinib可完全抑制肿瘤生长。按这种剂量处理，在21天内，有<10%肿瘤损失。Lapatinib可有效抑制人类移植瘤BT474 和HN5 的生长。

激酶实验

In vitro kinase assays: The IC50 values for inhibition of enzyme activity are generated by measuring inhibition of phosphorylation of a peptide substrate. The intracellular kinase domains of EGFR and ErbB2 are purified from a baculovirus expression system. EGFR and ErbB2 reactions are performed in 96-well polystyrene round-bottomed plates in a final volume of 45 μL. Reaction mixtures contain 50 mM 4-morpholinepropanesulfonic acid (pH 7.5), 2 mM MnCl2, 10 μM ATP, 1 μCi of [γ33P] ATP/reaction, 50 μM Peptide A [Biotin-(amino hexonoic acid)-EEEEYFELVAKKK-CONH2], 1 mM dithiothreitol, and 1 μL of DMSO containing serial dilutions of Lapatinib beginning at 10 μM. The reaction is initiated by adding the indicated purified type-1 receptor intracellular domain. The amount of enzyme added is 1 pmol/reaction (20 nM). Reactions are terminated after 10 minutes at 23°C by adding 45 μL of 0.5% phosphoric acid in water. The terminated reaction mix (75 μL) is transferred to phosphocellulose filter plates. The plates are filtered and washed three times with 200 μL of 0.5% phosphoric acid. Scintillation cocktail (50 μL) is added to each well, and the assay is quantified by counting in a Packard Topcount. IC50 values are generated from 10-point dose-response curves.

细胞实验

Cells are exposed to various concentrations of Lapatinib for 72 hours. Relative cell number is estimated using methylene blue staining. The absorbance at 620 nm is read in a Spectra microplate reader. Cell death and cell cycle analysis are assessed by propidium iodide staining and antibody detection of incorporated BrdUrd and staining with propidium iodide.(Only for Reference)

细胞系： HFF, MCF-7, T47D, A-431, HN5, BT474, N87, CaLu-3, HB4a, and HB4a c5.2 cells

动物实验

动物模型：CD-1 nude femice implanted s.c. with HN5 cells, and C.B-17 SCID femice implanted s.c. with BT474 cells

分子量

581.06

分子式

C29H26ClFN4O4S

CAS

231277-92-2

溶解度

DMSO: 93 mg/mL (160.1 mM)

Ethanol: <1 mg/mL

Water: <1 mg/mL

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.